Reference Intervals in Healthy Adult Ugandan Blood Donors and Their Impact on Conducting International Vaccine Trials

Abstract

BackgroundClinical trials are increasingly being conducted internationally. In order to ensure enrollment of healthy participants and proper safety evaluation of vaccine candidates, established reference intervals for clinical tests are required in the target population.Methodology/Principal FindingsWe report a reference range study conducted in Ugandan adult blood bank donors establishing reference intervals for hematology and clinical chemistry parameters. Several differences were observed when compared to previously established values from the United States, most notably in neutrophils and eosinophils.Conclusions/SignificanceIn a recently conducted vaccine trial in Uganda, 31 percent (n = 69) of volunteers screened (n = 223) were excluded due to hematologic abnormalities. If local reference ranges had been employed, 83% of those screened out due to these abnormalities could have been included in the study, drastically reducing workload and cost associated with the screening process. In addition, toxicity tables used in vaccine and drug trial safety evaluations may need adjustment as some clinical reference ranges determined in this study overlap with grade 1 and grade 2 adverse events.

Reference Values for Some Renal Function Parameters for Adult Population in North-Rift Valley, Kenya

“…Similar findings were noted in Rwanda [8]. Sex differences in UA have been previously documented by Roche Diagnostics, Eller et al, Saathoff et al and Khan et al [2,4,5,9] which could be due to the influence of sex hormones resulting in differences in body mass between sexes. The general absence of sex differences for BUN, CA, and PHOS in this study agrees with those reported in the reagent manufacturer's reference range values [2]; the result is similar to studies done in Pakistan [10], an indication that these parameters are not influenced by sex hormones.…”

“…Male creatinine values for the current study were lower than those for America, Kericho and Kuwait groups [2,5,11], greater than those for Tanzanian population [3] and comparable with those of the Uganda group [4]. North Rift female creatinine values were higher than the America, Mbeya, and Kampala [2][3][4] but lower than those for Kericho populations [5]. Among the electrolytes, NA and [4,13].…”

“…The North Rift Kenya values for urea were lower than those of America and Kuwait [2,11], comparable with the Kampala, Uganda group [4] but slightly higher than those for Mbeya, Tanzania and Kericho, Kenya [3,5]. Male creatinine values for the current study were lower than those for America, Kericho and Kuwait groups [2,5,11], greater than those for Tanzanian population [3] and comparable with those of the Uganda group [4].…”

“…North Rift female creatinine values were higher than the America, Mbeya, and Kampala [2][3][4] but lower than those for Kericho populations [5]. Among the electrolytes, NA and [4,13]. The higher reference range value for CREAT compared to those of other locations could be due to genetic factors and environmental factors.…”

“…Laboratory reference values for populations from western countries are widely published in scientific literature [2], textbooks and on the worldwide web. However, there is a general lack of published data regarding laboratory parameters for populations living in tropical sub-Saharan Africa [3] and the few studies that have been undertaken have indicated differences in reference values of African populations compared to those derived from western populations [3][4][5][6]. These differences suggest the need for the development of locally derived reference values.…”